2-Bromothiazole → HCID 23062573, compound

HRID 491803Notes

Reaction equation

HRID 491803 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([NH:9][C:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[O:12][C:11]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=2)=[O:20])=[O:8])[CH2:3][CH2:2]1.Br[C:30]1[S:31][CH:32]=[CH:33][N:34]=1.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CC(O)CC.CN(C)C(=O)C>[S:31]1[CH:32]=[CH:33][N:34]=[C:30]1[N:1]1[CH2:6][CH2:5][CH:4]([C:7]([NH:9][C:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[O:12][C:11]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=2)=[O:20])=[O:8])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 764302-Bromothiazole2×HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 23062699HCID 23062699, compound

Product 1

HCID 23062573HCID 23062573, compound

Reagents, catalysts & solvents 2

HCID 6568(+-)-2-ButanolSolventHCID 31374DimethylacetamideSolvent

Procedure

3-[(Piperidin-4-yl)carbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (100 mg) obtained in Example 228 is suspended in 2-butanol (5 ml), and thereto are added 2-bromothiazole (113 μl) and N,N-diisopropylethylamine (131 μl), and the mixture is heated under reflux for 24 hours. To the reaction solution are added 2-bromothiazole (57 μl) and N,N-dimethylacetamide (2 ml), and the mixture is further heated under reflux for 24 hours. To the reaction solution is poured a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The organic layer is washed with water and a saturated brine, and dried over sodium sulfate. The solvent is evaporated under reduced pressure, and the resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=3/1, then ethyl acetate) to give 3-[[1-(2-thiazolyl)piperidin-4-yl]-carbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (38 mg). This product is further treated with hydrogen chloride in dioxane to give the title compound (25 mg).

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 24 hours
  3. temperaturethe mixture is further heated
  4. temperatureunder reflux for 24 hours
  5. extractionthe mixture is extracted with chloroform
  6. washThe organic layer is washed with water
  7. dry with materiala saturated brine, and dried over sodium sulfate
  8. customThe solvent is evaporated under reduced pressure
  9. customthe resulting residue is purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-c46648ff19de472f8f51f22b61e58594
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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